Italian National Surveillance of Alcohol-Based Hand Rub Consumption in a Healthcare Setting-A Three-Year Analysis: 2020-2022.

Background/Objectives: Hand hygiene (HH) is pivotal in mitigating infectious disease transmission and enhancing public health outcomes. This study focuses on detailing the national surveillance system for alcohol-based hand rub (ABHR) consumption in healthcare facilities across Italy, presenting results from a comprehensive three-year evaluation period, from 2020 to 2022. It aims to delineate this surveillance system and report on ABHR consumption trends in various Regions/Autonomous Provinces (Rs/APs). Methods: ABHR consumption data, collected through the ABHR Italian national surveillance system, coordinated by the Istituto Superiore di Sanità (ISS), were analyzed. Statistical methods, e.g., the Mann-Whitney test, were used to assess trends in ABHR consumption, expressed in liters per 1000 patient days (L/1000PD). Results: The results show significant variation in ABHR consumption across Rs/APs and over the years studied. National median ABHR consumption decreased from 2020 to 2022, with a significant reduction from a median of 24.5 L/1000PD in 2020 to 20.4 L/1000PD in 2021 and 15.6 L/1000PD in 2022. Conclusions: The decline in ABHR consumption raises concerns about the ongoing adherence to HH practices in Italian healthcare settings. This underscores the essential role that systematic ABHR monitoring and improved surveillance play in enhancing HH compliance, suggesting that sustained and strategic efforts are fundamental to uphold high standards of hygiene and to effectively respond to fluctuating ABHR usage trends over time. Further research is needed to explore barriers to effective ABHR use and to develop targeted strategies to improve HH practices.

Risk of breakthrough infection and hospitalisation after COVID-19 primary vaccination by HIV status in four Italian regions during 2021.

BACKGROUND: As of 2024, vaccination remains the main mitigation measure against COVID-19, but there are contradictory results on whether people living with HIV (PLWH) are less protected by vaccines than people living without HIV (PLWoH). In this study we compared the risk of SARS-CoV-2 infection and COVID-19 hospitalisation following full vaccination in PLWH and PLWoH. METHODS: We linked data from the vaccination registry, the COVID-19 surveillance system and from healthcare/pharmacological registries in four Italian regions. We identified PLWH fully vaccinated (14 days post completion of the primary cycle) and matched them at a ratio of 1:4 with PLWoH by week of vaccine administration, age, sex, region of residence and comorbidities. Follow-up started on January 24, 2021, and lasted for a maximum of 234 days. We used the Kaplan-Meier estimator to calculate the cumulative incidence of infection and COVID-19 hospitalisation in both groups, and we compared risks using risk differences and ratios taking PLWoH as the reference group. RESULTS: We matched 42,771 PLWH with 171,084 PLWoH. The overall risk of breakthrough infection was similar in both groups with a rate ratio (RR) of 1.10 (95% confidence interval (CI):0.80-1.53). The absolute difference between groups at the end of the study period was 8.28 events per 10,000 person-days in the PLWH group (95%CI:-18.43-40.29). There was a non-significant increase the risk of COVID-19 hospitalisation among PLWH (RR:1.90; 95%CI:0.93-3.32) which corresponds to 6.73 hospitalisations per 10,000 individuals (95%CI: -0.57 to 14.87 per 10,000). CONCLUSIONS: Our findings suggest PLWH were not at increased risk of breakthrough SARS-CoV-2 infection or COVID-19 hospitalisation following a primary cycle of mRNA vaccination.

Differences urban versus non-urban trends in mortality from ischemic heart disease and diabetes in Italy and Spain, 2003-2019.

BACKGROUND AND AIMS: In recent years, mortality from ischemic heart disease and diabetes has decreased. There is an inequality in mortality reduction between urban and non-urban areas. This study aims to estimate the trend in mortality from ischemic heart disease and diabetes mellitus in urban and non-urban areas in Italy and Spain, throughout the first two decades of the 21st century. METHODS: Deaths and population data by age and sex, according to the area de residence, were obtained from the National Institutes of Statistics. Annual age-standardized mortality rates from ischemic heart disease and diabetes mellitus were calculated from 2003 to 2019, in each of the two areas of residence in both countries. The average annual percentage change (APC) in the mortality rate in each area was estimated using linear regression models and taking age-standardized mortality rates as dependent variable. RESULTS: Mortality rates from both causes of death decreased between the beginning and the end of the period analysed. In Italy, the APC in was -4.0% and -3.6% in mortality rate from ischemic heart disease and -1.5% and -1.3% in mortality rate from diabetes mellitus, in urban and non-urban areas, respectively. In Spain, the APC in was -4.4% and -3.7% in mortality rate from ischemic heart disease and -3.3% and -2.0% in mortality rate from diabetes mellitus, in urban and non-urban areas, respectively. CONCLUSION: Mortality from ischemic heart disease and mortality from diabetes have shown a greater reduction in urban than in non-urban areas since the first years of the 21st century in Spain and Italy.

This study evaluated the trend in mortality from ischemic heart disease and diabetes in urban and non-urban areas in two Southern European countries, Italy and Spain, throughout the first two decades of the 21st century.A reduction in mortality from diabetes and ischemic heart disease was observed in both urban and non-urban areas in both countries.Residents in urban areas showed a greater reduction in mortality than residents in non-urban areas. The mortality advantage found in non-urban areas at the beginning of the study disappeared at the end of it or even mortality became higher in non-urban areas.

The impact of underreported infections on vaccine effectiveness estimates derived from retrospective cohort studies.

BACKGROUND: Surveillance data and vaccination registries are widely used to provide real-time vaccine effectiveness (VE) estimates, which can be biased due to underreported (i.e. under-ascertained and under-notified) infections. Here, we investigate how the magnitude and direction of this source of bias in retrospective cohort studies vary under different circumstances, including different levels of underreporting, heterogeneities in underreporting across vaccinated and unvaccinated, and different levels of pathogen circulation. METHODS: We developed a stochastic individual-based model simulating the transmission dynamics of a respiratory virus and a large-scale vaccination campaign. Considering a baseline scenario with 22.5% yearly attack rate and 30% reporting ratio, we explored fourteen alternative scenarios, each modifying one or more baseline assumptions. Using synthetic individual-level surveillance data and vaccination registries produced by the model, we estimated the VE against documented infection taking as reference either unvaccinated or recently vaccinated individuals (within 14 days post-administration). Bias was quantified by comparing estimates to the known VE assumed in the model. RESULTS: VE estimates were accurate when assuming homogeneous reporting ratios, even at low levels (10%), and moderate attack rates (<50%). A substantial downward bias in the estimation arose with homogeneous reporting and attack rates exceeding 50%. Mild heterogeneities in reporting ratios between vaccinated and unvaccinated strongly biased VE estimates, downward if cases in vaccinated were more likely to be reported and upward otherwise, particularly when taking as reference unvaccinated individuals. CONCLUSIONS: In observational studies, high attack rates or differences in underreporting between vaccinated and unvaccinated may result in biased VE estimates. This study underscores the critical importance of monitoring data quality and understanding biases in observational studies, to more adequately inform public health decisions.

Effectiveness against severe COVID-19 of a seasonal booster dose of bivalent (original/Omicron BA.4-5) mRNA vaccines in persons aged ≥60 years: Estimates over calendar time and by time since administration during prevalent circulation of different Omicron subvariants, Italy, 2022-2023.

Evaluating how a COVID-19 seasonal vaccination program performed might help to plan future campaigns. This study aims to estimate the relative effectiveness (rVE) against severe COVID-19 of a seasonal booster dose over calendar time and by time since administration. We conducted a retrospective cohort analysis among 13,083,855 persons aged ≥60 years who were eligible to receive a seasonal booster at the start of the 2022-2023 vaccination campaign in Italy. We estimated rVE against severe COVID-19 (hospitalization or death) of a seasonal booster dose of bivalent (original/Omicron BA.4-5) mRNA vaccines by two-month calendar interval and at different times post-administration. We used multivariable Cox regression models, including vaccination as time-dependent exposure, to estimate adjusted hazard ratios (HR) and rVEs as [(1-HR)X100]. The rVE of a seasonal booster decreased from 64.9% (95% CI: 59.8-69.4) in October-November 2022 to 22.0% (95% CI: 15.4-28.0) in April-May 2023, when the majority of vaccinated persons (67%) had received the booster at least 4-6 months earlier. During the epidemic phase with prevalent circulation of the Omicron BA.5 subvariant, rVE of a seasonal booster received ≤90 days earlier was 83.0% (95% CI: 79.1-86.1), compared to 37.4% (95% CI: 25.5-47.5) during prevalent circulation of the Omicron XBB subvariant. During the XBB epidemic phase, rVE was estimated at 15.8% (95% CI: 9.1-20.1) 181-369 days post-administration of the booster dose. In all the analyses we observed similar trends of rVE between persons aged 60-79 and those ≥80 years, although estimates were somewhat lower for the oldest group. A seasonal booster dose received during the vaccination campaign provided additional protection against severe COVID-19 up to April-May 2023, after which the incidence of severe COVID-19 was much reduced. The results also suggest that the Omicron XBB subvariant might have partly escaped the immunity provided by the seasonal booster targeting the original and Omicron BA.4-5 strains of SARS-CoV-2.

Spatial spread of COVID-19 during the early pandemic phase in Italy.

Quantifying the potential spatial spread of an infectious pathogen is key to defining effective containment and control strategies. The aim of this study is to estimate the risk of SARS-CoV-2 transmission at different distances in Italy before the first regional lockdown was imposed, identifying important sources of national spreading. To do this, we leverage on a probabilistic model applied to daily symptomatic cases retrospectively ascertained in each Italian municipality with symptom onset between January 28 and March 7, 2020. Results are validated using a multi-patch dynamic transmission model reproducing the spatiotemporal distribution of identified cases. Our results show that the contribution of short-distance ( ≤ 10 k m ) transmission increased from less than 40% in the last week of January to more than 80% in the first week of March 2020. On March 7, 2020, that is the day before the first regional lockdown was imposed, more than 200 local transmission foci were contributing to the spread of SARS-CoV-2 in Italy. At the time, isolation measures imposed only on municipalities with at least ten ascertained cases would have left uncontrolled more than 75% of spillover transmission from the already affected municipalities. In early March, national-wide restrictions were required to curb short-distance transmission of SARS-CoV-2 in Italy.

Socioeconomic Inequalities in SARS-CoV-2 Infection and COVID-19 Health Outcomes in Urban Italy During the COVID-19 Vaccine Rollout, January-November 2021.

This study analysed the evolution of the association of socioeconomic deprivation (SED) with SARS-CoV-2 infection and COVID-19 outcomes in urban Italy during the vaccine rollout in 2021. We conducted a retrospective cohort analysis between January and November 2021, comprising of 16,044,530 individuals aged ≥ 20 years, by linking national COVID-19 surveillance system data to the Italian SED index calculated at census block level. We estimated incidence rate ratios (IRRs) of infection and severe COVID-19 outcomes by SED tercile relative to the least deprived tercile, over three periods defined as low (0-10%); intermediate (> 10-60%) and high (> 60-74%) vaccination coverage. We found patterns of increasing relative socioeconomic inequalities in infection, hospitalisation and death as COVID-19 vaccination coverage increased. Between the low and high coverage periods, IRRs for the most deprived areas increased from 1.09 (95%CI 1.03-1.15) to 1.28 (95%CI 1.21-1.37) for infection; 1.48 (95%CI 1.36-1.61) to 2.02 (95%CI 1.82-2.25) for hospitalisation and 1.57 (95%CI 1.36-1.80) to 1.89 (95%CI 1.53-2.34) for death. Deprived populations in urban Italy should be considered as vulnerable groups in future pandemic preparedness plans to respond to COVID-19 in particular during mass vaccination roll out phases with gradual lifting of social distancing measures.

Effect of an enhanced public health contact tracing intervention on the secondary transmission of SARS-CoV-2 in educational settings: The four-way decomposition analysis.

Background: The aim of our study was to test the hypothesis that the community contact tracing strategy of testing contacts in households immediately instead of at the end of quarantine had an impact on the transmission of SARS-CoV-2 in schools in Reggio Emilia Province. Methods: We analysed surveillance data on notification of COVID-19 cases in schools between 1 September 2020 and 4 April 2021. We have applied a mediation analysis that allows for interaction between the intervention (before/after period) and the mediator. Results: Median tracing delay decreased from 7 to 3.1 days and the percentage of the known infection source increased from 34-54.8% (incident rate ratio-IRR 1.61 1.40-1.86). Implementation of prompt contact tracing was associated with a 10% decrease in the number of secondary cases (excess relative risk -0.1 95% CI -0.35-0.15). Knowing the source of infection of the index case led to a decrease in secondary transmission (IRR 0.75 95% CI 0.63-0.91) while the decrease in tracing delay was associated with decreased risk of secondary cases (1/IRR 0.97 95% CI 0.94-1.01 per one day of delay). The direct effect of the intervention accounted for the 29% decrease in the number of secondary cases (excess relative risk -0.29 95%-0.61 to 0.03). Conclusions: Prompt contact testing in the community reduces the time of contact tracing and increases the ability to identify the source of infection in school outbreaks. Although there are strong reasons for thinking it is a causal link, observed differences can be also due to differences in the force of infection and to other control measures put in place. Funding: This project was carried out with the technical and financial support of the Italian Ministry of Health - CCM 2020 and Ricerca Corrente Annual Program 2023.

COVID-19 vaccination effectiveness in the population of Friuli Venezia Giulia, North-East Italy. Control of bias associated with divergent compliance to policies in a test-negative case-control study.

BACKGROUND: Vaccine effectiveness (VE) studies consolidate knowledge of real-world effectiveness in different contexts. However, methodological issues may undermine their conclusions: to assess the VE against COVID-19 within the Italian population, a specific threat to validity is related to the consequences of divergent compliance to the Green Pass policy. METHODS: To address this challenge we conducted a test negative case-control (TNCC) study and multiple sensitivity analysis among residents aged ≥ 12 in Friuli Venezia Giulia Region (FVG), North-east Italy, from February 1, 2021 to March 31, 2022. Information regarding 211,437 cases of COVID-19 infection and 845,748 matched controls was obtained from the regional computerized health database. The investigation considered: COVID-19 infection, hospitalization, and death. Multiple conditional logistic regressions adjusted for covariates were performed and VE was estimated as (1-OR COVID-19vaccinated vs. unvaccinated)x100. Mediation analyses were carried out to offset potential collider variables, particularly, the number of swabs performed after the introduction of pandemic restrictions. RESULTS: Full-cycle VE against infection decreased from 96% (95% CI: 96, 97) in the Alpha period to 43% (95% CI: 42, 45) in the Omicron period. Booster dose raised the protection in Omicron period to 67% (95% CI: 66, 67). Against the evasive Omicron variant, the protection of the booster dose was 87% (95% CI: 83, 90) for hospitalization and 90% (95% CI: 82, 95) for death. The number of swabs performed was included as a covariate in the adjustments, and the mediation analysis confirmed that it was a strong mediator between vaccination and COVID-19-related outcomes. CONCLUSIONS: The study suggests that, under similar TNCC settings, mediation analysis and adjustment for number of diagnostic tests should be included, as an effective approach to the challenge of differential testing behavior that may determine substantial selection bias. This correction allowed us to align with results from other studies that show how full-cycle VE against infection was initially high but decreased over time by variant circulation, counterbalanced by booster dose that raised protection across variants and outcome severity.

Estimated Effectiveness of a Primary Cycle of Protein Recombinant Vaccine NVX-CoV2373 Against COVID-19.

Importance: Protein recombinant vaccine NVX-CoV2373 (Novavax) against COVID-19 was authorized for its use in adults in late 2021, but evidence on its estimated effectiveness in a general population is lacking. Objective: To estimate vaccine effectiveness of a primary cycle with NVX-CoV2373 against SARS-CoV-2 infection and symptomatic COVID-19. Design, Setting, and Participants: Retrospective cohort study linking data from the national vaccination registry and the COVID-19 surveillance system in Italy during a period of Omicron predominance. All adults starting a primary vaccination with NVX-CoV2373 between February 28 and September 4, 2022, were included, with follow-up ending on September 25, 2022. Data were analyzed in February 2023. Exposures: Partial (1 dose only) vaccination and full vaccination (2 doses) with NVX-CoV-2373. Main Outcomes and Measures: Notified SARS-CoV-2 infection and symptomatic COVID-19. Poisson regression models were used to estimate effectiveness against both outcomes. Adjusted estimated vaccine effectiveness was calculated as (1 - incidence rate ratio) × 100. Results: The study included 20 903 individuals who started the primary cycle during the study period. Median (IQR) age of participants was 52 (39-61) years, 10 794 (51.6%) were female, and 20 592 participants (98.5%) had no factors associated with risk for severe COVID-19. Adjusted estimated vaccine effectiveness against notified SARS-CoV-2 infection in those partially vaccinated with NVX-CoV2373 was 23% (95% CI, 13%-33%) and was 31% (95% CI, 22%-39%) in those fully vaccinated. Estimated vaccine effectiveness against symptomatic COVID-19 was 31% (95% CI, 16%-44%) in those partially vaccinated and 50% (95% CI, 40%-58%) in those fully vaccinated. Estimated effectiveness during the first 4 months after completion of the primary cycle decreased against SARS-CoV-2 infection but remained stable against symptomatic COVID-19. Conclusions and Relevance: This cohort study found that, in an Omicron-dominant period, protein recombinant vaccine NVX-CoV2373 was associated with protection against SARS-CoV-2 infection and symptomatic COVID-19. The use of this vaccine could remain an important element in reducing the impact of the SARS-CoV-2 pandemic.

Estimating SARS-CoV-2 infections and associated changes in COVID-19 severity and fatality.

Background: The difficulty in identifying SARS-CoV-2 infections has not only been the major obstacle to control the COVID-19 pandemic but also to quantify changes in the proportion of infections resulting in hospitalization, intensive care unit (ICU) admission, or death. Methods: We developed a model of SARS-CoV-2 transmission and vaccination informed by official estimates of the time-varying reproduction number to estimate infections that occurred in Italy between February 2020 and 2022. Model outcomes were compared with the Italian National surveillance data to estimate changes in the SARS-CoV-2 infection ascertainment ratio (IAR), infection hospitalization ratio (IHR), infection ICU ratio (IIR), and infection fatality ratio (IFR) in five different sub-periods associated with the dominance of the ancestral lineages and Alpha, Delta, and Omicron BA.1 variants. Results: We estimate that, over the first 2 years of pandemic, the IAR ranged between 15% and 40% (range of 95%CI: 11%-61%), with a peak value in the second half of 2020. The IHR, IIR, and IFR consistently decreased throughout the pandemic with 22-44-fold reductions between the initial phase and the Omicron period. At the end of the study period, we estimate an IHR of 0.24% (95%CI: 0.17-0.36), IIR of 0.015% (95%CI: 0.011-0.023), and IFR of 0.05% (95%CI: 0.04-0.08). Conclusions: Since 2021, changes in the dominant SARS-CoV-2 variant, vaccination rollout, and the shift of infection to younger ages have reduced SARS-CoV-2 infection ascertainment. The same factors, combined with the improvement of patient management and care, contributed to a massive reduction in the severity and fatality of COVID-19.

SARS-CoV-2 transmission patterns in educational settings during the Alpha wave in Reggio-Emilia, Italy.

Different monitoring and control policies have been implemented in schools to minimize the spread of SARS-CoV-2. Transmission in schools has been hard to quantify due to the large proportion of asymptomatic carriers in young individuals. We applied a Bayesian approach to reconstruct the transmission chains between 284 SARS-CoV-2 infections ascertained during 87 school outbreak investigations conducted between March and April 2021 in Italy. Under the policy of reactive quarantines, we found that 42.5% (95%CrI: 29.5-54.3%) of infections among school attendees were caused by school contacts. The mean number of secondary cases infected at school by a positive individual during in-person education was estimated to be 0.33 (95%CrI: 0.23-0.43), with marked heterogeneity across individuals. Specifically, we estimated that only 26.0% (95%CrI: 17.6-34.1%) of students and school personnel who tested positive during in-person education caused at least one secondary infection at school. Positive individuals who attended school for at least 6 days before being isolated or quarantined infected on average 0.49 (95%CrI: 0.14-0.83) secondary cases. Our findings provide quantitative insights on the contribution of school transmission to the spread of SARS-CoV-2 in young individuals. Identifying positive cases within 5 days after exposure to their infector could reduce onward transmission at school by at least 30%.

Relative effectiveness of bivalent Original/Omicron BA.4-5 mRNA vaccine in preventing severe COVID-19 in persons 60 years and above during SARS-CoV-2 Omicron XBB.1.5 and other XBB sublineages circulation, Italy, April to June 2023.

During predominant circulation of SARS-CoV-2 Omicron XBB.1.5 and other XBB sublineages (April-June 2023), we found that a second or third booster of Comirnaty bivalent Original/Omicron BA.4-5 mRNA vaccine, versus a first booster received at least 120 days earlier, was effective in preventing severe COVID-19 for more than 6 months post-administration in persons 60 years and above. In view of autumn 2023 vaccination campaigns, use of bivalent Original/Omicron BA.4-5 mRNA vaccines might be warranted until monovalent COVID-19 vaccines targeting Omicron XBB.1 sublineages become available.

Socio-Economic Factors Associated with Ethnic Disparities in SARS-CoV-2 Infection and Hospitalization.

BACKGROUND: There is evidence that non-Italians presented higher incidence of infection and worse health outcomes if compared to native populations in the COVID-19 pandemic. The aim of the study was to compare Italian- and non-Italian-born health outcomes, accounting for socio-economic levels. METHODS: We analyzed data relative to 906,463 people in Umbria (Italy) from 21 February 2020 to 31 May 2021. We considered the National Deprivation Index, the Urban-Rural Municipalities Index and the Human Development Index (HDI) of the country of birth. We used a multilevel logistic regression model to explore the influence of these factors on SARS-CoV-2 infection and hospitalization rates. Diagnosis in the 48 h preceding admission was an indicator of late diagnosis among hospitalized cases. RESULTS: Overall, 54,448 persons tested positive (6%), and 9.7% of them were hospitalized. The risk of hospital admission was higher among non-Italians and was inversely related to the HDI of the country of birth. A diagnosis within 48 h before hospitalization was more frequent among non-Italians and correlated to the HDI level. CONCLUSIONS: COVID-19 had unequal health outcomes among the population in Umbria. Reduced access to primary care services in the non-Italian group could explain our findings. Policies on immigrants' access to primary healthcare need to be improved.

Relative effectiveness of monovalent and bivalent mRNA boosters in preventing severe COVID-19 due to omicron BA.5 infection up to 4 months post-administration in people aged 60 years or older in Italy: a retrospective matched cohort study.

BACKGROUND: Limited evidence is available on the additional protection conferred by second mRNA vaccine boosters against severe COVID-19 caused by omicron BA.5 infection, and whether the adapted bivalent boosters provide additional protection compared with the monovalent ones. In this study, we aimed to estimate the relative effectiveness of a second booster with monovalent or bivalent mRNA vaccines against severe COVID-19 in Italy. METHODS: Linking data from the Italian vaccination registry and the SARS-CoV-2 surveillance system, between Sept 12, 2022, and Jan 7, 2023, we matched 1:1 each person aged 60 years or older receiving a second booster with a person who had received the first booster only at least 120 days earlier. We used hazard ratios, estimated through Cox proportional hazard models, to compare the hazard of severe COVID-19 between the first booster group and each type of second booster (monovalent mRNA vaccine targeting the original strain of SARS-CoV-2, bivalent mRNA vaccine targeting the original strain plus omicron BA.1 [bivalent original/BA.1], and bivalent mRNA vaccine targeting the original strain plus omicron BA.4 and BA.5 [bivalent original/BA.4-5]). Relative vaccine effectiveness (rVE) was calculated as (1-hazard ratio) × 100. FINDINGS: We analysed a total of 2 129 559 matched pairs. The estimated rVE against severe COVID-19 with the bivalent original/BA.4-5 booster was 50·6% (95% CI 46·0-54·8) in the overall time interval 14-118 days post-administration. Overall, rVE was 49·3% (43·6-54·4) for the bivalent original/BA.1 booster and 26·9% (11·8-39·3) for the monovalent booster. For the bivalent original/BA.4-5 booster, we did not observe relevant differences in rVE between the 60-79-year age group (overall, 53·6%; 46·8-59·5) and those aged 80 years or older (overall, 48·3%; 41·9-54·0). INTERPRETATION: These findings suggest that a second booster with mRNA vaccines provides additional protection against severe COVID-19 due to omicron BA.5 (the predominant circulating subvariant in Italy during the study period) in people aged 60 years or older. Although rVE decreased over time, a second booster with the original/BA.4-5 mRNA vaccine, currently the most used in Italy, was found to be still providing protection 4 months post-administration. FUNDING: NextGenerationEU-MUR-PNRR Extended Partnership initiative on Emerging Infectious Diseases (project number PE00000007, INF-ACT). TRANSLATION: For the Italian translation of the abstract see Supplementary Materials section.

The Impact of Rotavirus Vaccination on Discharges for Pediatric Gastroenteritis in Italy: An Eleven Year (2009-2019) Nationwide Analysis.

In Italy, despite the documented positive effects of rotavirus (RV) vaccination on reducing the burden of RV disease, an updated national assessment of its impact on clinical outcomes is still lacking. This study aims to analyze the implementation of RV vaccination in Italy, evaluating its impact on discharges for acute pediatric gastroenteritis (AGE). A retrospective analysis, including hospital discharge records and data on vaccination coverage for children aged 0-71 months from 2009 to 2019, was conducted. We examined trends in hospital discharge standardized incidence before and after vaccine introduction using a negative binomial mixture model with fixed effects to evaluate the impact of universal vaccination. The percentage of vaccination coverage increased over the years, from <5% between 2009 and 2013 to 26% in 2017, reaching 70% in 2019. The standardized incidence of discharges decreased over the period from 16.6/100,000 inhabitants in 2009-2013 to 9.9/100,000 inhabitants in 2018-2019. In this phase, about 15% of the estimated hospital discharges were avoided compared with those estimated in the first phase. The implementation of RV vaccination reduced AGE incidence discharges in children aged 0-71 months. Further efforts are needed to continue monitoring the vaccination effect over time and to increase vaccination coverage.

Geographic heterogeneity of the epidemiological impact of the COVID-19 pandemic in Italy using a socioeconomic proxy-based classification of the national territory.

Objectives: This study aimed to evaluate the differences in incidence, non-intensive care unit (non-ICU) and intensive care unit (ICU) hospital admissions, and COVID-19-related mortality between the "inner areas" of Italy and its metropolitan areas. Study design: Retrospective population-based study conducted from the beginning of the pandemic in Italy (20 February 2020) to 31 March 2022. Methods: The municipalities of Italy were classified into metropolitan areas, peri-urban/intermediate areas and "inner areas" (peripheral/ultra-peripheral). The exposure variable was residence in an "inner area" of Italy. Incidence of diagnosis of SARS-CoV-2 infection, non-ICU and ICU hospital admissions and death within 30 days from diagnosis were the outcomes of the study. COVID-19 vaccination access was also evaluated. Crude and age-standardized rates were calculated for all the study outcomes. The association between the type of area of residence and each outcome under study was evaluated by calculating the ratios between the standardized rates. All the analyses were stratified by period of observation (original Wuhan strain, Alpha variant, Delta variant, Omicron variant). Results: Incidence and non-ICUs admissions rates were lower in "inner areas." ICU admission and mortality rates were much lower in "inner areas" in the early phases of the pandemic, but this protection progressively diminished, with a slight excess risk observed in the "inner areas" during the Omicron period. The greater vaccination coverage in metropolitan areas may explain this trend. Conclusion: Prioritizing healthcare planning through the strengthening of the primary prevention policies in the peripheral areas of Italy is fundamental to guarantee health equity policies.

[Long-term exposure to ambient air pollution and the incidence of SARS-CoV-2 infections in Italy: The EpiCovAir study]. / Esposizione a lungo termine a inquinamento dell'aria ambiente e incidenza di infezioni di SARS-CoV-2 in Italia: lo studio EpiCovAir.

BACKGROUND: after the outbreak of the SARS-CoV-2 pandemic in 2020, several waves of pandemic cases have occurred in Italy. The role of air pollution has been hypothesized and investigated in several studies. However, to date, the role of chronic exposure to air pollutants in increasing incidence of SARS-CoV-2 infections is still debated. OBJECTIVES: to investigate the association between long-term exposure to air pollutants and the incidence of SARS-CoV-2 infections in Italy. DESIGN: a satellite-based air pollution exposure model with 1-km2 spatial resolution for entire Italy was applied and 2016-2019 mean population-weighted concentrations of particulate matter < 10 micron (PM10), PM <2.5 micron (PM2.5), and nitrogen dioxide (NO2) was calculated to each municipality as estimates of chronic exposures. A principal component analysis (PCA) approach was applied to 50+ area-level covariates (geography and topography, population density, mobility, population health, socioeconomic status) to account for the major determinants of the spatial distribution of incidence rates of SARS-CoV-2 infection. Detailed information was further used on intra- and inter-municipal mobility during the pandemic period. Finally, a mixed longitudinal ecological design with the study units consisting of individual municipalities in Italy was applied. Generalized negative binomial models controlling for age, gender, province, month, PCA variables, and population density were estimated. SETTING AND PARTICIPANTS: individual records of diagnosed SARS-2-CoV-2 infections in Italy from February 2020 to June 2021 reported to the Italian Integrated Surveillance of COVID-19 were used. MAIN OUTCOME MEASURES: percentage increases in incidence rate (%IR) and corresponding 95% confidence intervals (95% CI) per unit increase in exposure. RESULTS: 3,995,202 COVID-19 cases in 7,800 municipalities were analysed (total population: 59,589,357 inhabitants). It was found that long-term exposure to PM2.5, PM10, and NO2 was significantly associated with the incidence rates of SARS-CoV-2 infection. In particular, incidence of COVID-19 increased by 0.3% (95%CI 0.1%-0.4%), 0.3% (0.2%-0.4%), and 0.9% (0.8%-1.0%) per 1 µg/m3 increment in PM2.5, PM10 and NO2, respectively. Associations were higher among elderly subjects and during the second pandemic wave (September 2020-December 2020). Several sensitivity analyses confirmed the main results. The results for NO2 were especially robust to multiple sensitivity analyses. CONCLUSIONS: evidence of an association between long-term exposure to ambient air pollutants and the incidence of SARS-CoV-2 infections in Italy was found.

SARS-CoV-2 Breakthrough Infections According to the Immune Response Elicited after mRNA Third Dose Vaccination in COVID-19-Naïve Hospital Personnel.

BACKGROUND: Vaccine-induced SARS-CoV-2-anti-spike antibody (anti-S/RBD) titers are often used as a marker of immune protection and to anticipate the risk of breakthrough infections, although no clear cut-off is available. We describe the incidence of SARS-CoV-2 vaccine breakthrough infections in COVID-19-free personnel of our hospital, according to B- and T-cell immune response elicited one month after mRNA third dose vaccination. METHODS: The study included 487 individuals for whom data on anti-S/RBD were available. Neutralizing antibody titers (nAbsT) against the ancestral Whuan SARS-CoV-2, and the BA.1 Omicron variant, and SARS-CoV-2 T-cell specific response were measured in subsets of 197 (40.5%), 159 (32.6%), and 127 (26.1%) individuals, respectively. RESULTS: On a total of 92,063 days of observation, 204 participants (42%) had SARS-CoV-2 infection. No significant differences in the probability of SARS-CoV-2 infection for different levels of anti-S/RBD, nAbsT, Omicron nAbsT, or SARS-CoV-2 T cell specific response, and no protective thresholds for infection were found. CONCLUSIONS: Routine testing for vaccine-induced humoral immune response to SARS-CoV-2 is not recommended if measured as parameters of 'protective immunity' from SARS-CoV-2 after vaccination. Whether these findings apply to new Omicron-specific bivalent vaccines is going to be evaluated.

Long-Term Exposure to Ambient Air Pollution and Mortality among Four Million COVID-19 Cases in Italy: The EpiCovAir Study.

BACKGROUND: The role of chronic exposure to ambient air pollutants in increasing COVID-19 fatality is still unclear. OBJECTIVES: The study aimed to investigate the association between long-term exposure to air pollutants and mortality among 4 million COVID-19 cases in Italy. METHODS: We obtained individual records of all COVID-19 cases identified in Italy from February 2020 to June 2021. We assigned 2016-2019 mean concentrations of particulate matter (PM) with aerodynamic diameter ≤10µm (PM10), PM with aerodynamic diameter ≤2.5µm (PM2.5), and nitrogen dioxide (NO2) to each municipality (n=7,800) as estimates of chronic exposures. We applied a principal component analysis (PCA) and a generalized propensity score (GPS) approach to an extensive list of area-level covariates to account for major determinants of the spatial distribution of COVID-19 case-fatality rates. Then, we applied generalized negative binomial models matched on GPS, age, sex, province, and month. As additional analyses, we fit separate models by pandemic periods, age, and sex; we quantified the numbers of COVID-19 deaths attributable to exceedances in annual air pollutant concentrations above predefined thresholds; and we explored associations between air pollution and alternative outcomes of COVID-19 severity, namely hospitalizations or accesses to intensive care units. RESULTS: We analyzed 3,995,202 COVID-19 cases, which generated 124,346 deaths. Overall, case-fatality rates increased by 0.7% [95% confidence interval (CI): 0.5%, 0.9%], 0.3% (95% CI: 0.2%, 0.5%), and 0.6% (95% CI: 0.5%, 0.8%) per 1 µg/m3 increment in PM2.5, PM10, and NO2, respectively. Associations were higher among elderly subjects and during the first (February 2020-June 2020) and the third (December 2020-June 2021) pandemic waves. We estimated ∼8% COVID-19 deaths were attributable to pollutant levels above the World Health Organization 2021 air quality guidelines. DISCUSSION: We found suggestive evidence of an association between long-term exposure to ambient air pollutants with mortality among 4 million COVID-19 cases in Italy. https://doi.org/10.1289/EHP11882.